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One potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury.    Methods   In vivo  microscopy was utilized in a surfactant deactivation porcine ARDS model to observe the effects of Vt and PEEP on alveolar mechanics. In phase I ( n  = 3), nine combinations of Vt and PEEP were evaluated to determine which combination resulted in the most and least alveolar instability. In phase II ( n  = 6), data from phase I were utilized to separate animals into two groups based on the combination of Vt and PEEP that caused the most alveolar stability (high Vt [15 cc/kg] plus low PEEP [5 cmH 2 O]) and least alveolar stability (low Vt [6 cc/kg] and plus PEEP [20 cmH 2 O]). The animals were ventilated for three hours following lung injury, with  in vivo  alveolar stability measured and VILI assessed by lung function, blood gases, morphometrically, and by changes in inflammatory mediators.    Results  High Vt/low PEEP resulted in the most alveolar instability and lung injury, as indicated by lung function and morphometric analysis of lung tissue. Low Vt/high PEEP stabilized alveoli, improved oxygenation, and reduced lung injury. There were no significant differences between groups in plasma or bronchoalveolar lavage cytokines or proteases.    Conclusion  A ventilatory strategy employing high Vt and low PEEP causes alveolar instability, and to our knowledge this is the first study to confirm this finding by direct visualization. These studies demonstrate that low Vt and high PEEP work synergistically to stabilize alveoli, although increased PEEP is more effective at stabilizing alveoli than reduced Vt. In this animal model of ARDS, alveolar instability results in lung injury (VILI) with minimal changes in plasma and bronchoalveolar lavage cytokines and proteases. This suggests that the mechanism of lung injury in the high Vt/low PEEP group was mechanical, not inflammatory in nature.

Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability